tbuckley/cabot-search huggingface dataset:
Sustained detection of type 2 poliovirus in London sewage between February and July, 2022, by enhanced environmental surveillance
Authors: Dimitra Klapsa, Thomas Wilton, Andrew Zealand, Erika Bujaki, Eugene Saxentoff, Catherine Troman, Alexander G Shaw, Alison Tedcastle, Manasi Majumdar, Ryan Mate, Joyce O Akello, Shahin Huseynov, Ali Zeb, Maria Zambon, Anita Bell, José Hagan, Matthew J Wade, Mary Ramsay, Nicholas C Grassly, Vanessa Saliba, Javier Martin
Journal: The Lancet (2022)
Personalized pancreatic cancer therapy: from the perspective of mRNA vaccine
Authors: Xing Huang, Gang Zhang, Tian-Yu Tang, Xiang Gao, Ting-Bo Liang
Journal: Military Medical Research (2022)

Abstract Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity, especially in genetic alteration and microenvironment. Conventional therapeutic strategies for pancreatic cancer usually suffer resistance, highlighting the necessity for personalized precise treatment. Cancer vaccines have become promising alternatives for pancreatic cancer treatment because of their multifaceted advantages including multiple targeting, minimal nonspecific effects, broad therapeutic window, low toxicity, and induction of persistent immunological memory. Multiple conventional vaccines based on the cells, microorganisms, exosomes, proteins, peptides, or DNA against pancreatic cancer have been developed; however, their overall efficacy remains unsatisfactory. Compared with these vaccine modalities, messager RNA (mRNA)-based vaccines offer technical and conceptional advances in personalized precise treatment, and thus represent a potentially cutting-edge option in novel therapeutic approaches for pancreatic cancer. This review summarizes the current progress on pancreatic cancer vaccines, highlights the superiority of mRNA vaccines over other conventional vaccines, and proposes the viable tactic for designing and applying personalized mRNA vaccines for the precise treatment of pancreatic cancer.
Safety of Right and Left Ventricular Endomyocardial Biopsy in Heart Transplantation and Cardiomyopathy Patients
Authors: Konstantinos Bermpeis, Giuseppe Esposito, Emanuele Gallinoro, Pasquale Paolisso, Dario Tino Bertolone, Davide Fabbricatore, Niya Mileva, Daniel Munhoz, John Buckley, Eric Wyffels, Jeroen Sonck, Carlos Collet, Emanuele Barbato, Bernard De Bruyne, Jozef Bartunek, Marc Vanderheyden
Journal: JACC Heart Failure (2022)
Hemodynamically-Guided Management of Heart Failure Across the Ejection Fraction Spectrum
Authors: Michael R. Zile, Mandeep R. Mehra, Anique Ducharme, Samuel F. Sears, Akshay S. Desai, Alan Maisel, Sara Paul, Frank Smart, Gillian Grafton, Sachin Kumar, Tareck O. Nossuli, Nessa Johnson, John Henderson, Philip B. Adamson, Maria Rosa Costanzo, JoAnn Lindenfeld
Journal: JACC Heart Failure (2022)

Hemodynamically-guided management using an implanted pulmonary artery pressure sensor is indicated to reduce heart failure (HF) hospitalizations in patients with New York Heart Association (NYHA) functional class II-III with a prior HF hospitalization or those with elevated natriuretic peptides. The authors sought to evaluate the effect of left ventricular ejection fraction (EF) on treatment outcomes in the GUIDE-HF (Hemodynamic-GUIDEd management of Heart Failure) randomized trial. The GUIDE-HF randomized arm included 1,000 NYHA functional class II-IV patients (with HF hospitalization within the prior 12 months or elevated natriuretic peptides adjusted for EF and body mass index) implanted with a pulmonary artery pressure sensor, randomized 1:1 to a hemodynamically-guided management group (treatment) or a control group (control). The primary endpoint was the composite of HF hospitalizations, urgent HF visits, and all-cause mortality at 12 months. The authors assessed outcomes by EF in guideline-defined subgroups ≤40%, 41%-49%, and ≥50%, within the trial specified pre–COVID-19 period cohort. There were 177 primary events (0.553/patient-year) in the treatment group and 224 events (0.682/patient-year) in the control group (HR: 0.81 [95% CI: 0.66-1.00]; P = 0.049); HF hospitalization was lower in the treatment vs control group (HR: 0.72 [95% CI: 0.57-0.92]; P = 0.0072). Within each EF subgroup, primary endpoint and HF hospitalization rates were lower in the treatment group (HR <1.0 across the EF spectrum). Event rate reduction by EF in the treatment groups was correlated with reduction in pulmonary artery pressures and medication changes. Hemodynamically-guided HF management decreases HF-related endpoints across the EF spectrum in an expanded patient population of patients with HF. (Hemodynamic-GUIDEd Management of Heart Failure [GUIDE-HF]; NCT03387813)
Mobilising hope to overcome climate despair
Authors: Howard Frumkin, Sophie Cook, Juliet Dobson, Kamran Abbasi
Journal: BMJ (2022)

It is impossible to ignore the damage humans have inflicted on our planet.2022 brought new record temperatures, floods, storms, wildfires, and droughts across the world. 1 These events threaten the health of humans, wildlife, and habitats and are wreaking permanent and irreversible destruction on earth systems.
Cardiovascular Drug Interactions With Nirmatrelvir/Ritonavir in Patients With COVID-19
Authors: Sonu Abraham, Anju Nohria, Tomas G. Neilan, Aarti Asnani, Anu Mariam Saji, Jui Shah, Tara Lech, Jason Grossman, George M. Abraham, Daniel P. McQuillen, David T. Martin, Paul E. Sax, Sourbha S. Dani, Sarju Ganatra
Journal: Journal of the American College of Cardiology (2022)
Prevalence, Incidence, Lifetime Risks, and Outcomes of Heart Failure in Asia
Authors: Chung-Lieh Hung, Tze-Fan Chao, Chuan-Tsai Tsai, Jo-Nan Liao, Su-Shen Lim, Ta-Chuan Tuan, Tzeng-Ji Chen, Yi-Hsin Chan, Shih-Ann Chen, Chern-En Chiang
Journal: JACC Heart Failure (2022)
Prediction of Survival After Implantation of a Fully Magnetically Levitated Left Ventricular Assist Device
Authors: Mandeep R. Mehra, Aditi Nayak, Alanna A. Morris, David E. Lanfear, Hassan Nemeh, Sapna Desai, Aditya Bansal, Cesar Guerrero-Miranda, Shelley Hall, Joseph C. Cleveland, Daniel J. Goldstein, Nir Uriel, Leway Chen, Stephen Bailey, Anelechi Anyanwu, Gerald Heatley, Joyce Chuang, Jerry D. Estep
Journal: JACC Heart Failure (2022)

Clinical trials inform on average efficacy, but individualized risk assessments for outcome prediction are important in guiding treatment implementation.The authors developed and validated a patient-specific risk score to predict survival at 1 and 2 years after HeartMate 3 (HM3) left ventricular assist device (LVAD) implantation.The MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) trial includes 2,200 HM3 LVAD patients in the pivotal trial and Continued Access Protocol study (2014-2018). The authors randomly assigned all patients to a derivation cohort (n = 1,540) or validation cohort (n = 660). Univariate mortality predictors were screened for potential model inclusion, stepwise selection was used to build the multivariable Cox proportional hazards regression model, and performance (discrimination and calibration) was evaluated.Age, prior cardiac surgery (coronary artery bypass grafting [CABG] or valve procedure), lower serum sodium, higher blood urea nitrogen (BUN), small left ventricular size, and right atrial pressure-to-pulmonary capillary wedge pressure (RAP/PCWP) ratio >0.6 were significant risk factors for mortality. Receiver-operating characteristic (ROC) analysis in the validation cohort demonstrated an area under the curve (AUC) of 0.76 (95% CI: 0.70-0.81) at 1 year and 0.71 (95% CI: 0.66-0.77) at 2 years. Calibration between predicted and observed survival of the risk quintiles was high, with Pearson correlation coefficients of 0.986 and 0.994 at 1 and 2 years, respectively. Patients were successfully stratified into tertiles with higher-than-average, average, and lower-than-average survival, and observed mortality risk increased by 2-fold from one tertile to the next.A practical, easy-to-use HM3 Survival Risk Score with 6 components was developed to accurately predict 1- and 2-year survival after HM3 LVAD implantation. The survival risk score can be used to provide individual survival estimates to facilitate shared decision making when considering HM3 LVAD therapy. (MOMENTUM 3 Trial Portfolio; NCT02224755, NCT02892955).
Chronic convection-enhanced delivery of topotecan for patients with recurrent glioblastoma: a first-in-patient, single-centre, single-arm, phase 1b trial
Authors: Eleonora F Spinazzi, Michael G Argenziano, Pavan S Upadhyayula, Matei A Banu, Justin A Neira, Dominique M O Higgins, Peter B Wu, Brianna Pereira, Aayushi Mahajan, Nelson Humala, Osama Al-Dalahmah, Wenting Zhao, Akshay V Save, Brian J A Gill, Deborah M Boyett, Tamara Marie, Julia L Furnari, Tejaswi D Sudhakar, Sylwia A Stopka, Michael S Regan, Vanessa Catania, Laura Good, Stergios Zacharoulis, Meenu Behl, Petros Petridis, Sachin Jambawalikar, Akiva Mintz, Angela Lignelli, Nathalie Y R Agar, Peter A Sims, Mary R Welch, Andrew B Lassman, Fabio M Iwamoto, Randy S D’Amico, Jack Grinband, Peter Canoll, Jeffrey N Bruce
Journal: The Lancet Oncology (2022)
Finerenone and Heart Failure Outcomes by Kidney Function/Albuminuria in Chronic Kidney Disease and Diabetes
Authors: Gerasimos Filippatos, Stefan D. Anker, Bertram Pitt, Peter Rossing, Amer Joseph, Peter Kolkhof, Marc Lambelet, Robert Lawatscheck, George L. Bakris, Luis M. Ruilope, Rajiv Agarwal
Journal: JACC Heart Failure (2022)

In patients with type 2 diabetes (T2D), risks of cardiovascular mortality and heart failure (HF) increase with decreasing kidney function (estimated glomerular filtration rate [eGFR]) and increasing albuminuria (urine albumin-to-creatinine ratio [UACR]). Finerenone, a selective, nonsteroidal mineralocorticoid receptor antagonist, improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and T2D in FIDELITY (Finerenone in Chronic Kidney Disease and Type 2 Diabetes: Combined FIDELIO-DKD and FIGARO-DKD Trial Programme Analysis). This study sought to evaluate the effects of finerenone on HF outcomes by eGFR and/or UACR categories. FIDELITY included 13,026 patients with T2D and CKD (UACR 30-5,000 mg/g and eGFR ≥25 mL/min/1.73 m2) randomized to finerenone or placebo. Time-to-event outcomes were first hospitalization for heart failure (HHF), cardiovascular death or first HHF, recurrent HHF, and cardiovascular death or recurrent HHF, analyzed in subgroups by baseline eGFR (<60 and ≥60 mL/min/1.73 m2) and/or UACR (<300 and ≥300 mg/g). Compared with placebo, finerenone significantly reduced risk of first HHF (HR: 0.78 [95% CI: 0.66-0.92]; P = 0.003), cardiovascular death or first HHF (HR: 0.83 [95% CI: 0.74-0.93]; P = 0.002), recurrent HHF (HR: 0.79 [95% CI: 0.64-0.96]; P = 0.021), and cardiovascular death or recurrent HHF (HR: 0.82 [95% CI: 0.72-0.95]; P = 0.006). The risk of outcomes increased across baseline eGFR and UACR categories; lowest incidences were seen in patients with an eGFR ≥60 mL/min/1.73 m2 and a UACR <300 mg/g. Finerenone improved HF outcomes irrespective of baseline eGFR and/or UACR categories (all P interaction values >0.10). Compared with placebo, finerenone improved HF-related outcomes in patients with CKD and T2D, with consistent benefits across eGFR and/or UACR categories. (Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease [FIDELIO-DKD], NCT02540993; Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Chronic Kidney Disease [FIGARO-DKD], NCT02545049)
Reply to the letter regarding the article ‘Dulaglutide and cardiovascular and heart failure outcomes in patients with and without heart failure: a <scp>post‐hoc</scp> analysis from the <scp>REWIND</scp> randomized trial’
Authors: Kelley R.H. Branch, Hertzel C. Gerstein, Jeffrey L. Probstfield
Journal: European Journal of Heart Failure (2022)
Enhanced mitochondrial DNA editing in mice using nuclear-exported TALE-linked deaminases and nucleases
Authors: Seonghyun Lee, Hyunji Lee, Gayoung Baek, Eunji Namgung, Joo Min Park, Sanghun Kim, Seongho Hong, Jin-Soo Kim
Journal: Genome biology (2022)

Abstract We present two methods for enhancing the efficiency of mitochondrial DNA (mtDNA) editing in mice with DddA-derived cytosine base editors (DdCBEs). First, we fused DdCBEs to a nuclear export signal (DdCBE-NES) to avoid off-target C-to-T conversions in the nuclear genome and improve editing efficiency in mtDNA. Second, mtDNA-targeted TALENs (mitoTALENs) are co-injected into mouse embryos to cleave unedited mtDNA. We generated a mouse model with the m.G12918A mutation in the MT-ND5 gene, associated with mitochondrial genetic disorders in humans. The mutant mice show hunched appearances, damaged mitochondria in kidney and brown adipose tissues, and hippocampal atrophy, resulting in premature death.
Effect of mindfulness-based programmes on elite athlete mental health: a systematic review and meta-analysis
Authors: Kearnan Myall, Jesus Montero-Marin, Paul Gorczynski, Nabeela Kajee, Rebecca Syed Sheriff, Robert Bernard, Eli Harriss, Willem Kuyken
Journal: British Journal of Sports Medicine (2022)

Objective To determine the effectiveness of mindfulness-based programmes (MBPs) on the mental health of elite athletes. Design Systematic review and meta-analysis. Data sources Eight online databases (Embase, PsycINFO, SPORTDiscus, MEDLINE, Scopus, Cochrane CENTRAL, ProQuest Dissertations &amp; Theses and Google Scholar), plus forward and backward searching from included studies and previous systematic reviews. Eligibility criteria for selecting studies Studies were included if they were randomised controlled trials (RCTs) that compared an MBP against a control, in current or former elite athletes. Results Of 2386 articles identified, 12 RCTs were included in this systematic review and meta-analysis, comprising a total of 614 elite athletes (314 MBPs and 300 controls). Overall, MBPs improved mental health, with large significant pooled effect sizes for reducing symptoms of anxiety (hedges g =−0.87, number of studies (n)=6, p=0.017, I 2 =90) and stress ( g =−0.91, n=5, p=0.012, I 2 =74) and increasing psychological well-being ( g =0.96, n=5, p=0.039., I 2 =89). Overall, the risk of bias and certainty of evidence was moderate, and all findings were subject to high estimated levels of heterogeneity. Conclusion MBPs improved several mental health outcomes. Given the moderate degree of evidence, high-quality, adequately powered trials are required in the future. These studies should emphasise intervention fidelity, teacher competence and scalability within elite sport. PROSPERO registration number CRD42020176654.
Proteome-wide Mendelian randomization in global biobank meta-analysis reveals multi-ancestry drug targets for common diseases
Authors: Huiling Zhao, Humaria Rasheed, Therese Haugdahl Nøst, Yoonsu Cho, Yi Liu, Laxmi Bhatta, Arjun Bhattacharya, Gibran Hemani, George Davey Smith, Ben Michael Brumpton, Wei Zhou, Benjamin M. Neale, Tom R. Gaunt, Jie Zheng
Journal: Cell Genomics (2022)

Proteome-wide Mendelian randomization (MR) shows value in prioritizing drug targets in Europeans but with limited evidence in other ancestries. Here, we present a multi-ancestry proteome-wide MR analysis based on cross-population data from the Global Biobank Meta-analysis Initiative (GBMI). We estimated the putative causal effects of 1,545 proteins on eight diseases in African (32,658) and European (1,219,993) ancestries and identified 45 and 7 protein-disease pairs with MR and genetic colocalization evidence in the two ancestries, respectively. A multi-ancestry MR comparison identified two protein-disease pairs with MR evidence in both ancestries and seven pairs with specific effects in the two ancestries separately. Integrating these MR signals with clinical trial evidence, we prioritized 16 pairs for investigation in future drug trials. Our results highlight the value of proteome-wide MR in informing the generalizability of drug targets for disease prevention across ancestries and illustrate the value of meta-analysis of biobanks in drug development.
Differential plasticity and fate of brain-resident and recruited macrophages during the onset and resolution of neuroinflammation
Authors: Karen De Vlaminck, Hannah Van Hove, Daliya Kancheva, Isabelle Scheyltjens, Ana Rita Pombo Antunes, Jonathan Bastos, Monica Vara-Perez, Leen Ali, Myrthe Mampay, Lauren Deneyer, Juliana Fabiani Miranda, Ruiyao Cai, Luc Bouwens, Dimitri De Bundel, Guy Caljon, Benoît Stijlemans, Ann Massie, Jo A. Van Ginderachter, Roosmarijn E. Vandenbroucke, Kiavash Movahedi
Journal: Immunity (2022)
NEPTUNE: Phase 3 Study of First-Line Durvalumab Plus Tremelimumab in Patients With Metastatic NSCLC
Authors: Gilberto de Castro, Naiyer A. Rizvi, Peter Schmid, Konstantinos Syrigos, Claudio Martin, Nobuyuki Yamamoto, Ying Cheng, Vladimir Moiseyenko, Yvonne Summers, Ihor Vynnychenko, Sung Yong Lee, Maciej Bryl, Alona Zer, Mustafa Erman, Constanta Timcheva, Rajiv Raja, Kirsha Naicker, Urban Scheuring, Jill Walker, Helen Mann, Vikram Chand, Tony Mok
Journal: Journal of Thoracic Oncology (2022)

NEPTUNE, a phase 3, open-label study, evaluated first-line durvalumab plus tremelimumab versus chemotherapy in metastatic NSCLC (mNSCLC).Eligible patients with EGFR and ALK wild-type mNSCLC were randomized (1:1) to first-line durvalumab (20 mg/kg every 4 weeks until progression) plus tremelimumab (1 mg/kg every 4 weeks for up to four doses) or standard chemotherapy. Randomization was stratified by tumor programmed death-ligand 1 expression (≥25% versus <25%), tumor histologic type, and smoking history. The amended primary end point was overall survival (OS) in patients with blood tumor mutational burden (bTMB) greater than or equal to 20 mutations per megabase (mut/Mb). Secondary end points included progression-free survival (PFS) in patients with bTMB greater than or equal to 20 mut/Mb and safety and tolerability in all treated patients.As of June 24, 2019, 823 patients were randomized (intention-to-treat [ITT]); 512 (62%) were bTMB-evaluable, with 129 of 512 (25%) having bTMB greater than or equal to 20 mut/Mb (durvalumab plus tremelimumab [n = 69]; chemotherapy [n = 60]). Baseline characteristics were balanced in the intention-to-treat. Among patients with bTMB greater than or equal to 20 mut/Mb, OS improvement with durvalumab plus tremelimumab versus chemotherapy did not reach statistical significance (hazard ratio 0.71 [95% confidence interval: 0.49-1.05; p = 0.081]; median OS, 11.7 versus 9.1 months); the hazard ratio for PFS was 0.77 (95% confidence interval, 0.51-1.15; median PFS, 4.2 versus 5.1 months). In the overall safety population, incidence of grade 3 or 4 treatment-related adverse events was 20.7% (durvalumab plus tremelimumab) and 33.6% (chemotherapy).NEPTUNE did not meet its primary end point of improved OS with durvalumab plus tremelimumab versus chemotherapy in patients with mNSCLC and bTMB greater than or equal to 20 mut/Mb. Despite the amended study design, with a resultant small primary analysis population, therapeutic activity was aligned with expectations based on mechanistic biology and previous studies.
Intelligent risk prediction in public health using wearable device data
Authors: Marium M. Raza, Kaushik P. Venkatesh, Joseph C. Kvedar
Journal: npj Digital Medicine (2022)

The importance of infection risk prediction as a key public health measure has only been underscored by the COVID-19 pandemic. In a recent study, researchers use machine learning to develop an algorithm that predicts the risk of COVID-19 infection, by combining biometric data from wearable devices like Fitbit, with electronic symptom surveys. In doing so, they aim to increase the efficiency of test allocation when tracking disease spread in resource-limited settings. But the implications of technology that applies data from wearables stretch far beyond infection monitoring into healthcare delivery and research. The adoption and implementation of this type of technology will depend on regulation, impact on patient outcomes, and cost savings.
Pathogenesis and treatment of non-alcoholic steatohepatitis and its fibrosis
Authors: Kuei-Chuan Lee, Pei-Shan Wu, Han-Chieh Lin
Journal: Clinical and Molecular Hepatology (2022)

The initial presentation of non-alcoholic steatohepatitis (NASH) is hepatic steatosis. The dysfunction of lipid metabolism within hepatocytes caused by genetic factors, diet, and insulin resistance causes lipid accumulation. Lipotoxicity, oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum stress would further contribute to hepatocyte injury and death, leading to inflammation and immune dysfunction in the liver. During the healing process, the accumulation of an excessive amount of fibrosis might occur while healing. During the development of NASH and liver fibrosis, the gut-liver axis, adipose-liver axis, and renin-angiotensin system (RAS) may be dysregulated and impaired. Translocation of bacteria or its end-products entering the liver could activate hepatocytes, Kupffer cells, and hepatic stellate cells, exacerbating hepatic steatosis, inflammation, and fibrosis. Bile acids regulate glucose and lipid metabolism through Farnesoid X receptors in the liver and intestine. Increased adipose tissue-derived non-esterified fatty acids would aggravate hepatic steatosis. Increased leptin also plays a role in hepatic fibrogenesis, and decreased adiponectin may contribute to hepatic insulin resistance. Moreover, dysregulation of peroxisome proliferator-activated receptors in the liver, adipose, and muscle tissues may impair lipid metabolism. In addition, the RAS may contribute to hepatic fatty acid metabolism, inflammation, and fibrosis. The treatment includes lifestyle modification, pharmacological therapy, and non-pharmacological therapy. Currently, weight reduction by lifestyle modification or surgery is the most effective therapy. However, vitamin E, pioglitazone, and obeticholic acid have also been suggested. In this review, we will introduce some new clinical trials and experimental therapies for the treatment of NASH and related fibrosis.